Abstract：
Acetamiprid (ACP) is a novel neonicotinoid insecticide used for controlling insect pests. Resveratrol (RSV) is a natural polyphenol that possesses anti-oxidant, anti-inflammatory and anti-apoptotic actions. The current research explores the mechanism of ACP-induced cardiotoxicity and the alleviative effects of RSV. Male rats were allocated to four groups of ten each. Rats were treated daily for 90 days via oral route. Control rats received distilled water, ACP rats received 25 mg acetamiprid/kg, RSV rats received 20 mg resveratrol/kg and ACP + RSV rats received both ACP and RSV. ACP exposure increased serum creatine phosphokinase activity and cardiac troponin level. It also induced oxidative stress, as evidenced by the glutathione reduction, and malondialdehyde elevation, as well as the detrimental histopathological and immunohistochemical changes in the myocardium. Gene expression analysis revealed down-regulation in the mRNA expression of the survival-related genes α7 nAChR, Erk and Bcl-2, and up-regulation in the apoptosis-related genes Jnk, Bax and Caspase-3. Conversely, the concomitant administration of ACP with RSV alleviated most of the aforementioned toxic impacts. It can be concluded that ACP induces cardiotoxicity by dysregulating the mRNA expression of α7 nAChR and its downstream targets. Additionally, RSV is proved to be a promising ameliorative agent against ACP-induced cardiotoxicity.
摘要：
啶虫脒（ACP）是一种新型的新烟碱类杀虫剂，用于控制害虫。白藜芦醇（RSV）是一种天然多酚，具有抗氧化剂，抗炎和抗凋亡作用。本研究探讨了ACP诱导的心脏毒性的机制和RSV的缓解作用。将雄性大鼠分为四组,每组10只。每天通过口服途径治疗大鼠90天。对照大鼠接受蒸馏水，ACP大鼠接受25mg啶虫脒/kg，RSV大鼠接受20mg白藜芦醇/kg,ACP+RSV大鼠接受ACP和RSV。ACP暴露会增加血清肌酸磷酸激酶活性和心肌肌钙蛋白水平。它还诱导氧化应激，正如谷胱甘肽还原所证明的那样，和丙二醛升高，以及心肌中有害的组织病理学和免疫组织化学变化。基因表达分析显示存活相关基因α7nAChR的mRNA表达下调,Erk和Bcl-2，以及凋亡相关基因Jnk的上调，Bax和Caspase-3。相反，ACP与RSV的同时给药减轻了上述大部分毒性影响.可以得出结论，ACP通过失调α7nAChR及其下游靶标的mRNA表达来诱导心脏毒性。此外,RSV被证明是针对ACP诱导的心脏毒性的有希望的改善剂。
